Abstract

Objective: To determinewhether treatment with interleukin-1 receptor antagonist (IL1-ra) would affect amniotic
fluid concentrations of tumor necrosis factor alpha (TNF-α) and prostaglandins or clinical or microbiological outcomes
in a model of ascending bacterial infection in pregnancy.

Methods: Timed pregnant New Zealand white rabbits at 70% of gestation underwent endoscopic inoculation of
the cervices with 106
– 107cfu Escherichia coli . Animals were randomly assigned in a blinded manner to a 5-h intravenous
infusion of human IL1-ra (10 mg/kg) or placebo beginning 1 – 2 h after inoculation. Blood was drawn fromthe
does for assay of serum IL1-ra concentration before inoculation, at mid-infusion, after the infusion ended and at
necropsy. At necropsy, temperature and cultures were taken, and aspirated amniotic fluid was pooled for assays of
TNF-α, prostaglandin E2
( PGE2) and IL1-ra.

Results: Serum IL1-ra concentrations rose to a mean of 2 mg/ml at mid-infusion and fell markedly after the infusion
to concentrations barely detectable at necropsy. Between the two groups, there were no significant differences in
the rates of fever or positive cultures or in amniotic fluid concentrations of PGE2 or TNF-α.One unique finding was
the demonstration that administration of human IL1-ra to the does resulted inmeasurable concentrationsof human
IL1-ra in the amniotic fluid.

Conclusions: Treatment with an intravenous infusion of human IL1-ra after cervical inoculation with E. coli did not
affect clinical or microbiological outcomes or amniotic fluid concentrations of TNF-α or PGE2. This experiment
provides the first demonstration of passageof human IL1-ra from the maternal bloodstreamto the amniotic fluid.